Nana-Sinkam Serge P, Hunter Melissa G, Nuovo Gerard J, Schmittgen Thomas D, Gelinas Richard, Galas David, Marsh Clay B
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Ohio State University Medical Center, Columbus, OH 43210, USA.
Am J Respir Crit Care Med. 2009 Jan 1;179(1):4-10. doi: 10.1164/rccm.200807-1042PP. Epub 2008 Sep 11.
Over the last 15 years, investigators have identified small noncoding RNAs as regulators of gene expression. One type of noncoding RNAs are termed microRNAs (miRNAs). miRNAs are evolutionary conserved, approximately 22-nucleotide single-stranded RNAs that target genes by inducing mRNA degradation or by inhibiting translation. miRNAs are implicated in many critical cellular processes, including apoptosis, proliferation, and differentiation. Furthermore, it is estimated that miRNAs may be responsible for regulating the expression of nearly one-third of the human genome. Despite the identification of greater than 500 mature miRNAs, very little is known about their biological functions and functional targets. In the last 5 years, researchers have increasingly focused on the functional relevance and role that miRNAs play in the pathogenesis of human disease. miRNAs are known to be important in solid organ and hematological malignancies, heart disease, as potential modulators of the immune response, and organ development. It is anticipated that miRNA analysis will emerge as an important complement to proteomic and genomic studies to further our understanding of disease pathogenesis. Despite the application of genomics and proteomics to the study of human lung disease, few studies have examined miRNA expression. This perspective is not meant to be an exhaustive review of miRNA biology but will provide an overview of both miRNA biogenesis and our current understanding of the role of miRNAs in lung disease as well as a perspective on the importance of integrating this analysis as a tool for identifying and understanding the biological pathways in lung-disease pathogenesis.
在过去15年里,研究人员已确定小非编码RNA是基因表达的调节因子。一类非编码RNA被称为微小RNA(miRNA)。miRNA在进化上是保守的,约22个核苷酸的单链RNA,通过诱导mRNA降解或抑制翻译来靶向基因。miRNA参与许多关键的细胞过程,包括细胞凋亡、增殖和分化。此外,据估计miRNA可能负责调节近三分之一的人类基因组的表达。尽管已鉴定出500多种成熟miRNA,但对其生物学功能和功能靶点却知之甚少。在过去5年里,研究人员越来越关注miRNA在人类疾病发病机制中的功能相关性和作用。已知miRNA在实体器官和血液系统恶性肿瘤、心脏病中作为免疫反应的潜在调节因子以及器官发育中都很重要。预计miRNA分析将成为蛋白质组学和基因组学研究的重要补充,以加深我们对疾病发病机制的理解。尽管基因组学和蛋白质组学已应用于人类肺部疾病的研究,但很少有研究检测miRNA表达。本文并非对miRNA生物学的详尽综述,而是将概述miRNA的生物合成以及我们目前对miRNA在肺部疾病中的作用的理解,并展望将这种分析作为识别和理解肺部疾病发病机制中的生物学途径的工具的重要性。